Carnosine (beta-alanyl-L-histidine) and carcinine (beta-alanylhistamine) are natural imidazole-containing compounds found in the non-protein fraction of mammalian tissues. Carcinine was synthesized by an original procedure and characterized. Both carnosine and carcinine (10-25 mM) are capable of inhibiting the catalysis of linoleic acid and phosphatidylcholine liposomal peroxidation (LPO) by the O2(-.)-dependent iron-ascorbate and lipid-peroxyl-radical-generating linoleic acid 13-monohydroperoxide (LOOH)-activated haemoglobin systems, as measured by thiobarbituric-acid-reactive substance. Carcinine and carnosine are good scavengers of OH. radicals, as detected by iron-dependent radical damage to the sugar deoxyribose. This suggests that carnosine and carcinine are able to scavenge free radicals or donate hydrogen ions. The iodometric, conjugated diene and t.l.c. assessments of lipid hydroperoxides (13-monohydroperoxide linoleic acid and phosphatidylcholine hydroperoxide) showed their efficient reduction and deactivation by carnosine and carcinine (10-25 mM) in the liberated and bound-to-artificial-bilayer states. This suggests that the peroxidase activity exceeded that susceptible to direct reduction with glutathione peroxidase. Imidazole, solutions of beta-alanine, or their mixtures with peptide moieties did not show antioxidant potential. Free L-histidine and especially histamine stimulated iron (II) salt-dependent LPO. Due to the combination of weak metal chelating (abolished by EDTA), OH. and lipid peroxyl radicals scavenging, reducing activities to liberated fatty acid and phospholipid hydroperoxides, carnosine and carcinine appear to be physiological antioxidants able to efficiently protect the lipid phase of biological membranes and aqueous environments.

Globally, tobacco use is associated with 5 million deaths per annum and is regarded as one of the leading causes of premature death. Major chronic disorders associated with smoking include cardiovascular diseases, several types of cancer, and chronic obstructive pulmonary disease (lung problems). Cigarette smoking (CS) generates a cumulative oxidative stress, which may contribute to the pathogenesis of chronic diseases. Mainstream and side stream gas-phase smoke each have about the same concentration of reactive free radical species, about 1 × 10(16) radicals per cigarette (or 5 × 10(14) per puff). This effect is critical in understanding the biologic effects of smoke. Several lines of evidence suggest that cigarette smoke constituents can directly activate vascular reactive oxygen species production. In this work we present multiple evidence that CS provide the important risk factors in many age-related diseases, and is associated with increased cumulative and systemic oxidative stress and inflammation. The cited processes are marked by increased white blood cell (leucocytes, WBCs) turnover. The data suggest an alteration of the circulating WBCs by CS, resulting in increased adherence to endothelial cells. Telomeres are complex DNA-protein structures located at the end of eukaryotic chromosomes. Telomere length shortens with biologic age in all replicating somatic cells. It has been shown that tobacco smoking enhances telomere shortening in circulating human WBCs. Telomere attrition (expressed in WBCs) can serve as a biomarker of the cumulative oxidative stress and inflammation induced by smoking and, consequently, show the pace of biologic aging. We originally propose that patented specific oral formulations of nonhydrolized carnosine and carcinine provide a powerful tool for targeted therapeutic inhibition of cumulative oxidative stress and inflammation and protection of telomere attrition associated with smoking. The longitudinal studies of the clinical population groups described in this study including elderly support the hypothesis that telomere length is a predictor of survival and therapeutic treatment requirement associated with smoking behavior.

Topical NAC shows potential for the treatment and prevention of cataracts.

No abstract

UV-spectrophotometry and fluorescent analysis were used to study lipid extracts from lenses, aqueous humour and blocks containing trabecular and Schlemms canal tissues, obtained from 49 eyes of patients with primary open-angle glaucoma (POAG). Accumulation of the primary, secondary, and end products of lipid peroxidation (LPO) (diene and triene conjugates, Schiff's bases) was noted in the studied extracts. Significant differences in the levels of all the mentioned LPO products in comparison with the control were observed. The data may be considered as an evidence of LPO participation in destruction of the trabecule and Schlemm's canal in POAG.

Reactive oxygen species (ROS) are of primary importance as they cause damage to lipids, proteins, and DNA either endogenously by cellular mechanism, or through exogenous exposure to environmental injury factors, including oxidation insult factors, such as tobacco smoke. Currently 46.3 million adults (25.7 percent of the population) are smokers. This includes 24 million men (28.1 percent of the total) and more than 22 million women (23.5 percent). The prevalence is highest among persons 25-44 years of age. Cigarette smokers have a higher risk of developing several chronic disorders. These include fatty buildups in arteries, several types of cancer and chronic obstructive pulmonary disease (lung problems). As peripheral leukocytes have been the main target of human telomere research, most of what is known about human telomere dynamics in vivo is based on these cells. Leukocyte telomere length (TL) is a complex trait that is shaped by genetic, epigenetic, and environmental determinants. In this article, we consider that smoking modifies leukocyte TL in humans and contributes to its variability among individuals, although the smoking effect on TL and its relation with other metabolic indices may accelerate biological aging and development of smoking-induced chronic diseases in a large human population-based cohorts with smoking behavior. Recent studies confirmed that individuals with shorter telomeres present a higher prevalence of arterial lesions and higher risk of cardiovascular disease mortality. This study originally suggests that efficient therapeutic protection of TL and structure in response to stresses that are known to reduce TL, such as oxidative damage or inflammation associated with tobacco smoking, would lead to better telomere maintenance. Recently, we have discovered the potential use of telomere-restorative imidazole-containing dipeptide (non-hydrolized carnosine, carcinine) based therapy for better survival of smokers. We conclude that a better therapeutic or nutritional maintenance of TL may confer healthy aging in smokers and exceptional longevity in regularly ROS-exposed human survivors.

No abstract

Lipid peroxidation (LPO) is a causative factor of cataract. The increased concentrations of primary molecular LPO products (diene conjugates, lipid hydroperoxides) and end fluorescent LPO products, were detected in the lipid moieties of the aqueous humor samples obtained from patients with senile and complicated cataracts as compared to normal donors. The degrees of lens clouding were assessed quantitatively by measuring the optical density indices and areas of equidensities using digital image analysis. Human cataractous lenses showed decreased activity of glutathione peroxidase (GPX, catalyzing reduction of organic hydroperoxides including hydroperoxides of lipids). The apparent Km for tert-butylhydroperoxide was 0.434 mM for human normal and cataractous lens GPX. When lenses were exposed for 1 h at 37 degrees C to linoleic acid hydroperoxide (LOOH, 0.5 mM) or egg phosphatidyl-choline hydroperoxide (PLOOH, 1 micro mol per 112 micro mol of phospholipid) in liposomes suspended in the incubation medium, normal, immature and mature human cataractous lenses showed a significant loss in the residual content of liberated LOOH to 62%, 38% or 17%, correspondingly, but little or no reduction was observed with PLOOH in liposomal membranes. Human, rabbit or mice transparent or immature cataractous lenses induced significantly more absorbance changes in conjugated diene, iodometric and TBA-reactive substance measurements when incubated with liposomal membranes which were decreased in the presence of free radical scavengers and antioxidant enzymes (EDTA, SOD, L-carnosine, chelated iron, catalase). Injection into the vitreous body of the rabbit eye of a suspension of liposomes prepared from phospholipids containing LPO products induced the development of posterior subcapsular cataract. Saturated liposomes did not cause clouding of the lens. This modelling of cataract was accompanied by accumulation of fluorescing LPO products in the vitreous body, aqueous humor and the lens and also by a fall in the concentration of GSH in the lens. The peroxidative damage to the lens cell membranes and biomolecules induced in the lack of reductive detoxification of phospholipid hydroperoxides is proposed as the triggering mechanism of cataractogenesis.